Epigenetic mechanisms interface environmental experiences with gene expression to ultimately influence neuronal function and behavior. Salient experiences occurring during early-life can uniquely manifest as persistent changes in behavior and cognition. Exercise, a highly potent environmental signal, promotes memory and hippocampal plasticity mechanisms, but little is known about the impact of exercise on the development of memory functions. Our lab has developed a unique mouse model of early-life exercise that implicates a “critical period” of exercise sufficient to enhance synaptic plasticity and persistently enable long-term spatial memory. I will discuss our current work aimed at identifying both synaptic and epigenetic mechanisms supporting the lasting effects of early-life exercise on the efficiency of hippocampal memory.